A Preliminary Study of Genetic Variation in the Dopaminergic and Serotonergic Systems and Genome-Wide Additive Genetic Effects on Depression Severity and Treatment Response

Abstract

Major depression is a heritable disorder that is commonly treated with selective serotonin reuptake inhibitors. However, no study has quantified the overlap in genetic effects between pretreatment depression severity and treatment response and the extent to which genetic effects could be attributed to variation in the dopaminergic and serotonergic systems (DA/5-HT). Data (N=1618) from the clinician-rated Hamilton Rating Scale of Depression and the clinician-rated Quick Inventory of Depressive Symptomatology were obtained from participants of European ancestry in the Sequenced Treatment Alternatives to Relieve Depression clinical trial. Genetic variants explained 31%–64% of the variance across assessments of pretreatment depression severity and treatment response. However, effects from the DA/5-HT systems genes were negligible. There was also limited evidence for genetic overlap for pretreatment depression severity and treatment response. Despite the clear genetic contributions to these depression phenotypes, different genetic factors may contribute to depression severity and treatment response.

Inclusion of genetic variants in an ensemble of gradient boosting decision trees does not improve the prediction of citalopram treatment response

“…For threshold-dependent metrics (accuracy, sensitivity, specificity), a probability threshold of 0.5 was used for classification. www.nature.com/scientificreports/ Given that citalopram treatment response appears to be modestly heritable, approximately 40% in this sample 4,5 , why did the inclusion of SNPs not improve the prediction of treatment response? It has been estimated that for complex traits, accurate prediction at the individual level is dependent on the heritability and prevalence of the complex trait.…”

“…Indeed, there was high variability in SNPs selected by the elastic-net during the k -fold cross-validation procedure. Other work taking a candidate gene 6 , 7 , candidate system approach 5 , or polygenic risk scores 11 have generally found similarly disappointing results for the prediction of antidepressant treatment response. Thus, genetic variation may be most useful for investigating the etiology of treatment response between groups of patients (e.g., responders vs non-responders) but may currently not be useful for deriving personalized predictions of treatment response 34 .…”

“…This effect is likely highly polygenic, as chromosome length was associated with proportion of variance attributable to the chromosome. Moreover, other work has demonstrated that the heritability of citalopram response was not attributable to genetic variants commonly associated with serotonergic and dopaminergic signaling 5 .…”

Exploring differences between gender expressions in exercise self-efficacy and outcome expectations for exercise in individuals with stroke

“…neither masculine or feminine gender expressions), thereby contributing to lower exerciserelated mastery experiences that are primary drivers of exercise self-efficacy [71]. Moreover, individuals with undifferentiated gender traits are more likely to be at a greater risk of mobility disability [51] and report greater levels of social anxiety [72] and depression [73], in contrast to other gender expressions. Indeed, low self-efficacy is often a precursor for social anxiety [74].…”